The broad objective of the proposed study is a more precise definition of potential additional muscle fatigue mechanisms beyond the traditional claim of neuromuscular junction failure, or depletion of energy supplies. Earlier work by the principal investigator has dealt with a fatigue mechanism which occurs as a result of high frequency stimulation of human muscle at frequencies high enough to match forces generated during maximal voluntary efforts. A tentative hypothesis has been made that Na ion depletion and K ion accumulation in the intercellular spaces (including the t-tubules) appear to interfere with action potential within the muscle cell. Such an occurrence is apparently avoided during maximal voluntary efforts by a natural reduction in the firing frequency of the motor neurons. Confirmation of these arguments will require measurement of electrical activity from both intact human and isolated curarized animal muscle preparations. Contractile force and muscle electrical activity (smooth, rectified surface EMG (SRE), and evoked compound surface action potentials (SAP), will be recorded simultaneously during both voluntary and stimulated isometric contractions. Comparisons between the results obtained using the two types of contraction (voluntary and stimulated) and between results obtained from the two muscle preparations (intact human and isolated) will allow use to determine to what extent fatigue is due to failure of (a) the muscle contractile mechanism, (b) the excitation-contraction coupling process, or (c) neuromuscular transmission and what influence changing behavior of the motor neuron may have on each. Additional experiments will be performed on intact human muscles to determine the underlying causes of any observed changes in the SRE and SAP as well as on isolated preparations to determine the effect of changing ionic environment, temperature, energy-dependent activities, etc. on action potential size and propagation when stimulated at different frequencies.